The SUSTAIN Study Compares the Effects of Sustained and Immediate-release Pramipexole on the noctUrnal Symptoms of paTients With Advanced ParkInsoN's Disease Who Also Take L-Dopa

This is an interventional treatment trial for Parkinson Disease Read More

Inclusion Criteria:

• Male or female patient with advanced idiopathic Parkinson's disease (PD) confirmed by at least bradykinesia and one of the following signs: resting tremor, rigidity.
• Diagnosed as Parkinson's disease, with at least 2 years' PD history.
• Of age ≥ 30 years at time of diagnosis.
• Modified Hoehn and Yahr stage of 2 to 4 at on-time.
• They must have clinically relevant sleep disturbances (i.e. Parkinson's Disease Sleep Scale 2nd version (PDSS-2) total score ≥18 at baseline).
• They must feel uncomfortable at night because they were unable to turn around in bed or move due to immobility (i.e. the scoring of question 9 in PDSS-2 ≥ 2, that means frequency is at least 2 to 3 days during the past week).
• They must have early morning off (i.e. the frequency of "feeling like bodily movements are poor when you wake up?" is at least 2 to 3 days during the past week).
• Patient must have motor fluctuations (at least 2 cumulative hours of off-time every day during waking hours, documented on a patient diary completed for 2 consecutive days before randomization visit).
• Patients must be treated with Levodopa combined with a Dopa-Decarboxylase-inhibitor (L-Dopa+) (i.e. standard and/or controlled release Levodopa/DDC inhibitor), or with a combination of L-Dopa+ and entacapone, at an optimized dose according to investigator's judgment, this dose being stable for at least 4 weeks prior to randomization visit.
• Patients must not have been treated with sustained release dopaminergic drug (i.e. sustained release Levodopa/Dopa-Decarboxylase (DDC) inhibitor) after supper, or any anti-PD medication after 9pm within 4 weeks prior to randomization visit.

• Patients must not have been treated with dopamine agonists within 4 weeks prior to randomization visit. A concomitant treatment with one or more of the following drugs will be allowed (at a stable dose for at least 4 weeks prior to randomization visit and the investigator does not intend to change this treatment during the treatment phase):

  • Anti-parkinsonian anticholinergics;
  • Selegiline, rasagiline, or other Monoamine Oxydase (MAO)-B-Inhibitor;
  • Amantadine;
  • Entacapone (or other Catechol-O-Methyltransferase (COMT)-Inhibitor).
• Male or female patients. Women of childbearing potential (WOCBP) and men able to father a child must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information.
• Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial.

Exclusion criteria:

• Secondary parkinsonian syndromes due to drugs (e.g., metoclopramide, flunarizine), metabolic disorders (e.g., Wilson's disease), encephalitis or degenerative diseases (e.g., progressive supranuclear palsy).
• Dementia, as defined by a Mini-Mental State Exam score < 24 at screening visit.
• Any psychiatric disorder according to DSM-V Diagnostic and Statistical Manual of Mental Disorders, 5th edition criteria that could prevent compliance or completion of the study and/or put the patient at risk if he/she takes part in the study.
• History of psychosis, except history of drug induced hallucinations (provided the investigator considers that participation to the trial would not represent a significant risk for the patient).
• History of deep brain stimulation.
• History of nucleus lesioning.
• Clinically significant electrocardiogram (ECG) abnormalities at screening visit, according to investigator's judgement.
• Clinically significant hypotension (i.e. supine systolic blood pressure < 90 mmHg) and/or symptomatic orthostatic hypotension (i.e. clinical symptoms of orthostatic hypotension associated with a decline ≥ 20 mmHg in systolic blood pressure and a decline ≥ 10 mmHg in diastolic blood pressure, at 1 minute after standing compared with the previous supine systolic and diastolic blood pressure obtained after 5 minutes of quiet rest) at screening or randomization visit.
• Major surgery (major according to the investigator's assessment) performed within 12 weeks prior to randomization or planned within 12 months after screening, e.g. hip replacement.
• Any other clinically significant disease, whether treated or not, that could put the patient at risk or could prevent compliance or completion of the study.
• Serious Sleep Apnea Hypopnea Syndrome (i.e. the scoring of question 15 in Parkinson's Disease Sleep Scale 2nd version (PDSS-2)≥ 3, that means frequency is at least 4 to 5 days during the past week )
• Any documented active or suspected malignancy or history of malignancy within 5 years prior to screening, except appropriately treated basal cell carcinoma of the skin or in situ carcinoma of uterine cervix.
• Serum levels of Aspartate Aminotransferase (AST)(SGOT), Alanine Aminotransferase (ALT)(SGPT), alkaline phosphatases or total bilirubin >2 ULN (on screening lab test).
• Patients with a creatinine clearance < 50 mL/min (estimated by the local lab / the investigator using the Modification of Diet in Renal Disease (MDRD, please refer to Appendix 10.1), and calculated on screening lab test).
• Any hypnotic medication within 4 weeks prior to the randomization visit (i.e. diazepam, clonazepam, estazolam, alprazolam, zolpidem, etc.).
• Any medication (including intra-muscular formulations) with central dopaminergic antagonist activity within 4 weeks prior to the randomization visit (i.e. typical neuroleptics, atypical antipsychotics, reserpine, methyldopa, centrally-active antiemetics, etc.).
• Any of the following drugs within 4 weeks prior to randomization visit: methylphenidate, cinnarizine, amphetamines.
• Flunarizine within 3 months prior to randomization visit.
• Known hypersensitivity to Pramipexole or its excipients.
• Patients who must or wish to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial.
• Previous enrolment in this trial.
• Currently enrolled in another investigational device or drug trial, or less than 30 days since ending another investigational device or drug trial(s), or receiving other investigational treatment(s).
• Chronic alcohol or drug abuse or any condition that, in the investigator's opinion, makes them an unreliable trial patient or unlikely to complete the trial.
• Women who are pregnant, nursing, or who plan to become pregnant in the trial.